The overall hypothesis of this Program Project Grant proposal is that in the process of regulating nuclear receptor (NR) activity, individual members of the steroid receptor coactivator (SRC) family coordinate the expression of subsets of NR target genes in a ligand and tissue-specific manner. This project will identify the role that specific SRC family members play in the regulation of a differential tissue response to specific steroid hormone responsive to estrogen, progesterone, and androgens, and to elucidate the effect of ablation of SRC-1, SRC-2/TIF-2, and SRC-3 on individual tissue transcriptional responses to these hormones. This will be accomplished in four Specific Aims: Specific Aim 1 will expression. Specific Aim 2 will investigate the involvement of SRC family members in the determine the participation of SRC family members in the regulation of mammary gland contribution to SRC family members to the regulation of uterine gene expression in response to progesterone and estrogen. The accomplishment of these Aims will facilitate the determination of the metabolic fingerprint of SRC function in the hormonal regulation of tissue physiology.